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In Vivo Expansion and Antitumor Activity of Coinfused CD28- and 4-1BB-Engineered CAR-T Cells in Patients with B Cell Leukemia.

Publication ,  Journal Article
Cheng, Z; Wei, R; Ma, Q; Shi, L; He, F; Shi, Z; Jin, T; Xie, R; Wei, B; Chen, J; Fang, H; Han, X; Rohrs, JA; Bryson, P; Liu, Y; Li, Q-J ...
Published in: Mol Ther
April 4, 2018

Several recent clinical trials have successfully incorporated a costimulatory domain derived from either CD28 or 4-1BB with the original CD3ζ T cell activating domain to form second-generation chimeric antigen receptors (CARs) that can increase the responsiveness and survival of CAR-engineered T (CAR-T) cells. However, a rigorous assessment of the individual benefits of these costimulatory components relative to the in vivo performance of infused T cells in patients is still lacking. Therefore, we have designed a study that allows us to investigate and compare the impact of different costimulatory signal domains on CAR-T cells in vivo. Patients with B cell leukemia were infused with a mixture of two types of CD19-specific CAR-T cells, individually bearing CD28 (28ζ) and 4-1BB (BBζ) costimulatory signaling domains. We found that such a clinical procedure was feasible and safe. Complete remission (CR) was observed in five of seven enrolled patients, with two patients exhibiting durable CR lasting more than 15 months. The in vivo expansion pattern of 28ζ and BBζ CAR-T cells varied significantly among individual patients. These results confirm a feasible method of comparing different CAR designs within individual patients, potentially offering objective insights that may facilitate the development of optimal CAR-T cell-based immunotherapies.

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Published In

Mol Ther

DOI

EISSN

1525-0024

Publication Date

April 4, 2018

Volume

26

Issue

4

Start / End Page

976 / 985

Location

United States

Related Subject Headings

  • Young Adult
  • Xenograft Model Antitumor Assays
  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • Treatment Outcome
  • T-Lymphocytes
  • Retroviridae
  • Receptors, Chimeric Antigen
  • Receptors, Antigen, T-Cell
  • Middle Aged
  • Mice, Transgenic
 

Citation

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Cheng, Z., Wei, R., Ma, Q., Shi, L., He, F., Shi, Z., … Wang, P. (2018). In Vivo Expansion and Antitumor Activity of Coinfused CD28- and 4-1BB-Engineered CAR-T Cells in Patients with B Cell Leukemia. Mol Ther, 26(4), 976–985. https://doi.org/10.1016/j.ymthe.2018.01.022
Cheng, Zhi, Runhong Wei, Qiuling Ma, Lin Shi, Feng He, Zixiao Shi, Tao Jin, et al. “In Vivo Expansion and Antitumor Activity of Coinfused CD28- and 4-1BB-Engineered CAR-T Cells in Patients with B Cell Leukemia.Mol Ther 26, no. 4 (April 4, 2018): 976–85. https://doi.org/10.1016/j.ymthe.2018.01.022.
Cheng Z, Wei R, Ma Q, Shi L, He F, Shi Z, et al. In Vivo Expansion and Antitumor Activity of Coinfused CD28- and 4-1BB-Engineered CAR-T Cells in Patients with B Cell Leukemia. Mol Ther. 2018 Apr 4;26(4):976–85.
Cheng, Zhi, et al. “In Vivo Expansion and Antitumor Activity of Coinfused CD28- and 4-1BB-Engineered CAR-T Cells in Patients with B Cell Leukemia.Mol Ther, vol. 26, no. 4, Apr. 2018, pp. 976–85. Pubmed, doi:10.1016/j.ymthe.2018.01.022.
Cheng Z, Wei R, Ma Q, Shi L, He F, Shi Z, Jin T, Xie R, Wei B, Chen J, Fang H, Han X, Rohrs JA, Bryson P, Liu Y, Li Q-J, Zhu B, Wang P. In Vivo Expansion and Antitumor Activity of Coinfused CD28- and 4-1BB-Engineered CAR-T Cells in Patients with B Cell Leukemia. Mol Ther. 2018 Apr 4;26(4):976–985.

Published In

Mol Ther

DOI

EISSN

1525-0024

Publication Date

April 4, 2018

Volume

26

Issue

4

Start / End Page

976 / 985

Location

United States

Related Subject Headings

  • Young Adult
  • Xenograft Model Antitumor Assays
  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • Treatment Outcome
  • T-Lymphocytes
  • Retroviridae
  • Receptors, Chimeric Antigen
  • Receptors, Antigen, T-Cell
  • Middle Aged
  • Mice, Transgenic